GRF Anologs.

摘要

Human pancreatic GRF and the hypothalamic GRFs for the human and several other mammalian species were earlier characterized and synthesized. The invention provides synthetic peptides which are potent stimulators of the release of pituitary GH in animals, including humans, and which have the formula: R<Sub>1</Sub>-R<Sub>2</Sub>-R<Sub>3</Sub>-Ala-R<Sub>5</Sub>-R<Sub>6</Sub>-R<Sub>7</Sub>-R<Sub>8</Sub>-R<Sub>9</Sub>-R<Sub>10</Sub>-R<Sub>11</Sub>-R<Sub>12</Sub>-R<Sub>13</Sub>-Leu-R<Sub>15</Sub>-GIn-Leu-R<Sub>18</Sub>-R<Sub>19</Sub>-R<Sub>20</Sub>-R<Sub>21</Sub>-Leu-Leu-Gln-Glu-R<Sub>26</Sub>-R<Sub>27</Sub>-R<Sub>28</Sub>-Arg-Y wherein R, is Tyr, D-Tyr, Met, Phe, D-Phe, Leu, His or D-His, which has either a C<Sup>a</Sup>Me or N<Sup>a</Sup>Me substitution or is unsubstituted; R<Sub>2</Sub> is Ala or D-Ala; R, is Asp or D-Asp; R<Sub>5</Sub> is lie or Leu; R<Sub>6</Sub> is Phe or Tyr; R, is Ser or Thr; R<Sub>5</Sub> is Ser, Asn, Thr or Gin; R, is Ala or Ser; R<Sub>10</Sub> is Tyr, Phe or Leu; R<Sub>11</Sub> in Arg, Om or Lys; R,, is Arg, Om or Lys; R<Sub>13</Sub> is Ile, Leu, Phe or Val; R<Sub>15</Sub> is Gly or Ala; R<Sub>18</Sub> is Ala or Ser; R<Sub>19</Sub> is Ser or Ala; R<Sub>20</Sub> is Arg, Om or Lys; R<Sub>21</Sub> is Arg, Om or Lys; R<Sub>26</Sub> is Leu, Ile, Val or Phe; R<Sub>27</Sub> is Nle, Nva or a natural amino acid; R<Sub>28</Sub> is Ala, Leu, Asn, Gin, or Ser; and Y is OH or NH<Sub>2</Sub>; provided however that at least four of the residues constituting R<Sub>s</Sub>, R<Sub>5</Sub>, R<Sub>7</Sub>, R<Sub>a</Sub>, R<Sub>9</Sub>, R,<Sub>o</Sub>, R<Sub>11</Sub>, R<Sub>12</Sub>, R<Sub>13</Sub>, R<Sub>15</Sub>, R<Sub>18</Sub>, R<Sub>19</Sub>, R<Sub>20</Sub>, R<Sub>21</Sub> and R<Sub>26</Sub> are different from the residues appearing in that respective position in the native molecule. These peptides as well as non- toxic salts thereof may be administered to animals, including humans and cold-blooded animals, to stimulate the release of GH and may be used diagnostically.